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Haemophilus influenzae infection

This page is about clinical aspects of the disease.  For microbiologic aspects of the causative organism(s), see Haemophilus influenzae.

For patient information about Haemophilus influenzae infection, click here | Haemophilus influenzae type b (Hib) vaccine, click here.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]
Synonyms and keywords: Hib disease

Overview

Overview

H.influenzae is a gram-negative, cocco-bacillary, facultatively anaerobic pathogenic bacterium that can cause infections in people of all ages ranging from mild, such as an ear infection, to severe, such as a bloodstream infection. It is a normal commensal of nose and throat and does not cause any infection under normal situations. But when the host defense mechanisms are weakened it invades the epithelium and disseminates to other parts of the body where it causes infection.[1]

Causes

Causes

This page is about microbiologic aspects of the organism(s).  For clinical aspects of the disease, see Haemophilus influenzae infection.

For additional information about other Haemophilus species, click here.
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Haemophilus influenzae, formerly called Pfeiffer’s bacillus or Bacillus influenzae, is a non-motile Gram-negative coccobacillus first described in 1892 by Richard Pfeiffer during an influenza pandemic. It is generally aerobic, but can grow as a facultative anaerobe. H. influenzae was mistakenly considered to be the cause of the common flu until 1933, when the viral etiology of the flu became apparent. Still, H. influenzae is responsible for a wide range of clinical diseases. Because of its small genome, H. influenzae became the first free-living organism with its entire genome sequenced. Its genome consists of 1,830,140 base pairs of DNA and contains 1740 genes. The method used was Whole genome shotgun. The sequencing project, completed and published in Science in 1995, was conducted at The Institute for Genomic Research.[1]

Serotypes

In 1930, 2 major categories of H. influenzae were defined: the unencapsulated strains and the encapsulated strains. The pathogenesis of H. influenzae infections is not completely understood, although the presence of the encapsulated type b (Hib) is known to be the major factor in virulence. Their capsule allows them to resist phagocytosis and complement-mediated lysis in the non-immune host. Unencapsulated strains are less invasive, but they are able to induce an inflammatory response that causes disease, such as epiglottitis. Vaccination with Hib conjugate vaccines is effective in preventing infection, and several vaccines are now available for routine use.

Diseases

Most strains of H. influenzae are opportunistic pathogens – that is, they usually live in their host without causing disease, but cause problems only when other factors (such as a viral infection or reduced immune function) create an opportunity. There are six generally recognized types of H. influenzae: a, b, c, d, e, and f.[2]

Naturally-acquired disease caused by H. influenzae seems to occur in humans only. In infants and young children, H. influenzae type b (Hib) causes bacteremia, and acute bacterial meningitis. Occasionally, it causes cellulitis, osteomyelitis, epiglottitis, and joint infections. Due to routine use of the Hib conjugate vaccine in the U.S. since 1990, the incidence of invasive Hib disease has decreased to 1.3/100,000 children. However, Hib remains a major cause of lower respiratory tract infections in infants and children in developing countries where vaccine is not widely used. Unencapsulated H. influenzae (non-B type) causes ear (otitis media) and eye (conjunctivitis) infections and sinusitis in children, and is associated with pneumonia.

Interaction with Streptococcus pneumoniae

Both H. influenzae and S. pneumoniae can be found in the upper respiratory system of humans. A study of competition in a laboratory revealed that, in a petri dish, S. pneumoniae always overpowered H. influenzae by attacking it with a hydrogen peroxide and stripping off the surface molecules H. influenzae needs for survival.

When both bacteria are placed together into a nasal cavity, within 2 weeks, only H. influenzae survives. When both are placed separately into a nasal cavity, each one survives. Upon examining the upper respiratory tissue from mice exposed to both bacteria species, an extraordinarily large number of neutrophils immune cells were found. In mice exposed to only one bacteria, the cells were not present.

Lab tests showed that neutrophils exposed to dead H. influenzae were more aggressive in attacking S. pneumoniae than unexposed neutrophils. Exposure to dead H. influenzae had no effect on live H. influenzae.

Two scenarios may be responsible for this response:

  1. When H. influenzae is attacked by S. pneumoniae, it signals the immune system to attack the S. pneumoniae
  2. The combination of the two species together triggers an immune system response that is not set off by either species individually.

It is unclear why H. influenzae is not affected by the immune response.[3]

References

  1. Fleischmann R, Adams M, White O, Clayton R, Kirkness E, Kerlavage A, Bult C, Tomb J, Dougherty B, Merrick J (1995). “Whole-genome random sequencing and assembly of Haemophilus influenzae Rd”. Science. 269 (5223): 496–512. PMID 7542800.
  2. Ryan KJ; Ray CG (editors) (2004). Sherris Medical Microbiology (4th ed. ed.). McGraw Hill. pp. pp. 396&ndash, 401. ISBN 0838585299.
  3. Lysenko E, Ratner A, Nelson A, Weiser J (2005). “The role of innate immune responses in the outcome of interspecies competition for colonization of mucosal surfaces”. PLoS Pathog. 1 (1): e1. PMID 16201010.
  4. 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 “Public Health Image Library (PHIL)”.


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Classification

Classification

H. influenzae, including Hib, can cause many different kinds of infections. These infections can range from mild ear infections to severe diseases, like bloodstream infections. When the bacteria invade parts of the body, like spinal fluid or blood, this is known as “invasive disease.” Invasive disease is usually severe and can sometimes result in death.
The most common types of invasive disease caused by H.influenza are:

The most common types of non-invasive disease caused by H.influenza are:

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
H influenza infection
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Infection due to capsulated H influenzae(Invasive)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Infection due to non-capsulated H influenzae(Non-invasive)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Meningitis
 
Cellulitis
 
 
 
 
 
Epiglottitis
 
Pneumonia
 
Pericarditis
 
Septic arthritis
 
 
 
otitis media
 
 
 
 
 
 
 
Conjunctivitis
Pathophysiology

Pathophysiology

The pathogenesis of H.influenzae infections can be described as follows:[2][3]

Transmission

  • Transmission is by direct contact or by inhalation of respiratory tract droplets.
  • Neonates can acquire the infection by aspiration of amniotic fluid or contact with genital tract secretions containing the bacteria.

Incubation period

The incubation period (time between exposure and first symptoms) of H. influenzae disease is not certain but could be as short as 7 days.

Seeding

Pathogenesis

  • The capsule of H influenza plays a key role in the pathogenesis of the all the capsulated H influenza infections.
  • The antiphagocytic nature of the Hib capsule makes it resistant to natural host phagocytic defense mechanisms and facilitating bacterial proliferation.
  • After proliferation, the bacterial load disseminates to various sites, including meninges, subcutaneous tissue, joints, pleura, pericardium, and lungs triggering an inflammatory response and subsequently activating the complement system.
  • Capsulated H influenza can penetrate the normal epithelium and are therefore responsible for invasive infections.
  • Non-capsulated are non-invasive but can still induce the inflammatory response similar to that of capsulated organisms
  • The Hib conjugate vaccine induces protection by inducing antibodies against the PRP capsule.
  • The Hib conjugate vaccine does not provide protection against Non-typable H influenza strains. Since the widespread use of the Hib conjugate vaccine, Non-typable H influenza strains has become more of a pathogen.
References

References

  1. “Pinkbook | Hib | Epidemiology of Vaccine Preventable Diseases | CDC”.
  2. Duell BL, Su YC, Riesbeck K (2016). “Host-pathogen interactions of nontypeable Haemophilus influenzae: from commensal to pathogen”. FEBS Lett. 590 (21): 3840–3853. doi:10.1002/1873-3468.12351. PMID 27508518.
  3. Close RM, Pearson C, Cohn J (2016). “Vaccine-preventable disease and the under-utilization of immunizations in complex humanitarian emergencies”. Vaccine. 34 (39): 4649–55. doi:10.1016/j.vaccine.2016.08.025. PMID 27527818.


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